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Updated: Dec 30, 2025
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Systemic Management for Nonmetastatic Castration-resistant Prostate Cancer: A Systematic Review and Network
Zefu Liu1, Tong Zhang2, Zikun Ma1
1Department of Urology, Cancer Center, Sun Yat-sen University.
Purpose:
To indirectly compare the efficacy and safety of systemic therapies used for patients with nonmetastatic castration-resistant prostate cancer (nmCRPC).
Methods:
The relevant randomized controlled trials were retrieved from PubMed and the Cochrane Library. Network meta-analyses were used to compare multiple drugs simultaneously for the outcomes of nmCRPC. Direct evidence in trials and indirect evidence across trials were combined by the network meta-analyses to estimate the treatment efficiency.
Outcome:
Eight studies were included in our research. For prostate-specific antigen progression-free survival, the rate of progression was significantly decreased following apalutamide, enzalutamide, bicalutamide+dutasteride, and bicalutamide treatment compared with placebo. Compared with placebo treatment, metastases-free survival was significantly increased in patients who received apalutamide (hazard ratio [HR]: 0.28, 95% confidence interval [CI]: 0.23-0.35), enzalutamide (HR: 0.29, 95% CI: 0.24-0.35), and darolutamide (HR: 0.42, 95% CI: 0.35-0.50). Direct comparison showed significant survival benefits in patients who received second-generation anti-androgen therapy (apalutamide, enzalutamide, and darolutamide: HR: 0.74, 95% CI: 0.61-0.91) compared with patients who received placebo. With respect to metastases-free survival, based on SUCRA analysis, there was 80% and 78% probability that apalutamide and enzalutamide were preferred treatment, while darolutamide was likely to be second-best choice. Compared with placebo, all agents were not associated with significantly higher likelihood of serious adverse events and grade 3 to 4 adverse events.
Conclusion:
Our outcomes support equivalent efficacy and similar risk of adverse effects between apalutamide, enzalutamide, and darolutamide, supporting the use of these antiandrogen agents in high-risk of progression nmCRPC.
Insights
Systemic therapies like apalutamide and enzalutamide show similar efficacy and safety for nonmetastatic castration-resistant prostate cancer (nmCRPC). These treatments significantly improve progression-free survival and reduce metastasis risk compared to placebo.
Area of Science:
- Oncology
- Pharmacology
Background:
- Nonmetastatic castration-resistant prostate cancer (nmCRPC) requires effective systemic therapies to manage disease progression.
- Evaluating and comparing the efficacy and safety of available treatments is crucial for optimizing patient care.
Purpose of the Study:
- To indirectly compare the efficacy and safety of various systemic therapies for patients diagnosed with nmCRPC.
- To provide evidence-based insights for treatment selection in nmCRPC management.
Main Methods:
- A systematic literature search was conducted in PubMed and the Cochrane Library for relevant randomized controlled trials.
- Network meta-analyses were employed to simultaneously compare multiple drugs for nmCRPC outcomes, integrating direct and indirect evidence.
- Efficacy outcomes included prostate-specific antigen progression-free survival and metastases-free survival; safety was assessed via adverse events.
Main Results:
- Apalutamide, enzalutamide, bicalutamide+dutasteride, and bicalutamide significantly decreased prostate-specific antigen progression compared to placebo.
- Metastases-free survival was significantly increased with apalutamide, enzalutamide, and darolutamide versus placebo.
- Second-generation anti-androgen therapies (apalutamide, enzalutamide, darolutamide) demonstrated significant survival benefits. Apalutamide and enzalutamide showed the highest probability of being preferred treatments for metastases-free survival.
Conclusions:
- Apalutamide, enzalutamide, and darolutamide exhibit comparable efficacy and similar safety profiles in nmCRPC patients.
- These anti-androgen agents are supported for use in nmCRPC patients at high risk of disease progression.
- The findings aid in informed treatment decisions for nmCRPC, emphasizing the benefits of newer anti-androgen therapies.
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